State Key Laboratory of Natural Medicines, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, 24 Tongjia Road, Nanjing, 210009, China.
Angew Chem Int Ed Engl. 2018 May 4;57(19):5389-5393. doi: 10.1002/anie.201801195. Epub 2018 Apr 14.
A telomerase-responsive DNA icosahedron was designed to precisely release caged platinum nanodrugs into cisplatin-resistance tumor cells for effective therapy. This DNA icosahedron was constructed from two pyramidal DNA cages connected with telomerase primers and telomeric repeats, and platinum nanodrugs were then encapsulated into the DNA structure. In the presence of telomerase, the primers are extended, leading to inner-chain substitution of the DNA icosahedron and subsequent release of the caged nanodrugs. This DNA icosahedron can precisely release caged nanodrugs in response to telomerase in tumor cells, giving enhanced anticancer efficacy in drug-resistant carcinoma and with reduced toxicity to normal tissues. We speculate that this precisely designed, well controlled DNA cage could be generalized to diverse anticancer drugs.
一种端粒酶响应的 DNA 二十面体被设计用于将笼状铂纳米药物精确递送到顺铂耐药肿瘤细胞中，以实现有效的治疗。该 DNA 二十面体由两个金字塔形 DNA 笼通过端粒酶引物和端粒重复序列连接而成，随后将铂纳米药物包封到 DNA 结构中。在端粒酶存在的情况下，引物被延伸，导致 DNA 二十面体的内链取代，随后笼状纳米药物被释放。这种 DNA 二十面体可以在肿瘤细胞中端粒酶的作用下精确释放笼状纳米药物，从而增强对耐药性癌的抗癌疗效，同时降低对正常组织的毒性。我们推测，这种经过精确设计、良好控制的 DNA 笼可以推广到多种抗癌药物中。
